title: Effect of raloxifene on disease activity and vascular biomarkers in patients with systemic lupus erythematosus: subgroup analysis of a double-blind randomized controlled trial.
abstract: OBJECTIVE
  The purpose of this study was to identify the effect of raloxifene on disease activity and vascular biomarkers in patients with systemic lupus erythematosus (SLE).
  
  
  METHODS
  Subgroup data were analyzed for postmenopausal female SLE patients who participated in a randomized controlled trial of raloxifene on glucocorticoid-induced osteoporosis. Patients who were receiving a stable daily dose of prednisolone (≤10 mg) for ≥6 months were assigned to receive raloxifene (60 mg/day) or placebo on top of calcium and vitamin D. Disease activity was assessed by the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA), SLE disease activity index (SLEDAI) and physicians' global assessment (PGA) every three months. Lupus flares were assessed by the SELENA flare instrument. Serial serum levels of homocysteine, high-sensitivity C-reactive protein (hsCRP) and soluble thrombomodulin (sTM) were measured.
  
  
  RESULTS
  A total of 62 patients (30 raloxifene, 32 placebo) were studied (age 52.5 ± 6.7 years; SLE duration 9.3 ± 7.6 years; menopause duration 7.2 ± 6.6 years). The SLEDAI at entry was 1.8 ± 2.3 (SLEDAI ≥ 6 in 8%). After 12 months, a significant gain in bone mineral density (BMD) of the lumbar spine (1.6%, p = 0.02), and reduction in bone resorption and formation markers was observed in the raloxifene but not in the placebo treated patients. The SELENA-SLEDAI and PGA scores area under the curve over 12 months were not significantly different between the two groups. There were three episodes of mild/moderate lupus flares (33% musculoskeletal, 33% dermatological) in the raloxifene group, compared to nine episodes of mild/moderate flares (27% musculoskeletal, 45% dermatological) in the placebo group (p = 0.11). The low density lipoprotein (LDL) cholesterol level increased significantly in the placebo but not raloxifene treated patients. No significant changes in homocysteine, hsCRP and sTM levels were observed in either group of patients.
  
  
  CONCLUSIONS
  Raloxifene significantly improves lumbar spine BMD in SLE patients but does not cause an increase in lupus activity or flares.
authors.affiliation: 1Department of Medicine, Tuen Mun Hospital, Hong Kong.
authors.forename: C C
authors.initials: CC
authors.lastname: Mok
authors.forename: Shirley K Y
authors.initials: SK
authors.lastname: Ying
authors.forename: K M
authors.initials: KM
authors.lastname: Ma
authors.forename: C K
authors.initials: CK
authors.lastname: Wong
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use; D002097:C-Reactive Protein / Q000378:metabolism; D004311:Double-Blind Method; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000627:therapeutic use; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D008159:Lumbar Vertebrae; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000503:physiopathology; D008875:Middle Aged; D017698:Postmenopause; D011239:Prednisolone / Q000627:therapeutic use; D020849:Raloxifene Hydrochloride / Q000494:pharmacology / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D004965:Estrogen Antagonists; D005938:Glucocorticoids; D006710:Homocysteine; D020849:Raloxifene Hydrochloride; D002097:C-Reactive Protein; D011239:Prednisolone
keywords: Lupus; activity; biomarkers; flares; selective estrogen modulation